[THE RELATIONSHIP AMONG BRONCHIAL HYPERSENSITIVITY, BRONCHIAL HYPER REACTIVITY, AND BRONCHIAL HYPERRESPONSIVENESS IN ASTOGRAPH].

BACKGROUND: Bronchial hyperresponsiveness testing is useful for diagnosing and predicting the risk of bronchial asthma attacks. The Astograph is a tidal breathing method often used in as bronchial provocation testing in Japan. The minimum methachorine dose (Dmin) indicates bronchial sensitivity and is used mainly as an index of bronchial hyperresponsiveness. However, Dmin does not measured hyperresponsiveness, it cannot be compared directly with PC20 in standard methods using FEV1. METHODS: We investigated the relationship among sensitivity, reactivity, and hyperresponsiveness with the Astograph. We recruited 142 patients with confirmed or suspected bronchial asthma from outpatient clinic at St. Marianna University School of Medicine, Yokohama City Seibu Hospital. We calculated Dmin, SGrs/Grscont, PD35Grs, and PD15Grs compared them as bronchial hyperresponsiveness indices. RESULTS: Subjects had suspected asthma (n=103), or required assessment of asthma remission (n=39). There were significant relationships between logDmin and logPD35Grs (r=0.838, p<0.001), and between parameters and SGrs/Grscont (log PD35Grs r=-0.504, p<0.001, strong, logDmin: r=-0.191, p=0.023, weaker). Among subjects positive for hypersensitivity, (Dmin<10), 38 (36.5%) showed negative hyperresponsiveness (PD35Grs>25). PD15Grs was a strongly and significantly correlated with Dmin and PD35Grs. The ROC curve to detect PD35Grs<25, showed that the cutoff of PD15Grs was 10.7 (AUC 0.983, sensitivity 0.984, specificity 0.905). CONCLUSION: In Astograph, evaluation of bronchial hyperresponsiveness, we focused on relationship differences between sensitivity and reactivity, and hyperresponsiveness. We revealed the usefulness of the PD15Grs evaluation method.

[A RESEARCH OF ADULT BRONCHIAL ASTHMATICS MANAGED UNDER YOKOHAMA CITY SEIBU HOSPITAL'S COORDINATED-CARE SYSTEM].

BACKGROUND: Our hospital in the western part of Yokohama City managed adult bronchial asthma patients via a coordinated care system with primary care clinics. The aim of the system is to provide effective daily and emergency medical care. METHODS: The study comprised 288 adult stable asthmatics (201 women) who were examined at Yokohama City Seibu Hospital between Jan 2009 and May 2018 and who were being managed under our coordinated care system at one of 80 primary clinics or hospitals. RESULTS: Of the 288 patients enrolled, 188 continued, 37 ended under management, and 63 dropped out from this system. The drop-out rate was highest at visit 1 (9%). The main reasons for end of cooperation under management were readjustment of asthma treatment and treatment for other diseases. The reasons for dropping out were low adherence, older age, and mild symptoms. There was a significant tendency in the frequency of patients who continued, ended under management, or dropped out (x2: 26.053, p=0.016), and the drop-out rate was significantly higher at visit 1. Comparing the characteristics of the patients who continued, ended under management, and dropped out within two visit, those who had dropped out were significantly younger (p=0.0067) and their duration of asthma was shorter (p=0.0009). The frequencies of emergency department visit and hospitalization were high until visit 2, but no significant trends were observed. CONCLUSION: Our coordinated care system managed 188 asthmatic patients (65.2%) properly. Patients with low adherence tended to drop out from the system at visit 1.

Japanese travel behavior trends and change under COVID-19 state-of-emergency declaration: Nationwide observation by mobile phone location data.

In the early stages of the COVID-19 pandemic, the Japan government could not impose strong restrictions such as lockdowns. Since there has been no such nation-wide behavioral analysis, we calculated indicators of nation-wide behavioral change using data based on mobile phone network.This study shows empirical facts and findings on behavioral changes under COVID-19 "state-of-emergency" declarations in Japan that are obtained by using mobile terminal network operational data. Results show that a significant reduction in trips and inter-prefectural travel was achieved without strong restrictions by the government. In addition, the population density index decreased by 20% and people avoided traveling to densely populated areas. This analysis shows that once people's behavior is changed by the declaration of a state of emergency, it does not return to normal immediately after the lifting of the declaration; rather, it recovers slowly.

Successful treatment with noninvasive positive-pressure ventilation based on the prediction of disease onset using CT and respiratory function tests in an elderly patient with relapsing polychondritis.

An 83-year-old man who had been receiving treatment for bronchial asthma since 62 years of age experienced difficulty breathing on exertion and was admitted to the hospital. On admission, computed tomography revealed tracheal wall thickening, while test results for antinuclear antibodies and anti-type II collagen antibodies were positive. Since a saddle nose deformity, malacia of the auricles and sensorineural deafness were also observed, relapsing polychondritis was diagnosed. Measuring the peak expiratory flow rate was useful in the early airway assessment. During the follow-up period, the patient's dyspnea worsened and noninvasive positive-pressure ventilation was introduced. As a result, the subjective symptoms improved.

The effect of risedronate (17.5 mg/week) treatment on quality of life in Japanese women with osteoporosis: a prospective observational study.

A prospective observational study to test the effects of risedronate 17.5 mg/week treatment on quality of life (QOL) of 1,363 Japanese female patients with osteoporosis showed QOL improvement after 12 weeks of administration. Comorbid factors such as ischemic heart disease, hip osteoarthritis, and higher values of FRAX blunted the effects of QOL of the treatment. Few studies have investigated the effect of osteoporosis treatment on QOL in relationship to comorbid factors other than osteoporosis and fracture. Efficacy was determined by changes over time in EQ-5D at baseline, at 12 and 24 weeks, and at the final assessment. Factors affecting changes in EQ-5D were evaluated with a multivariate analysis. Safety was determined by assessing the incident rate of adverse events. The improvement of EQ-5D compared to baseline was observed as significant after 12 weeks of treatment (p < 0.001). The greatest improvement was observed in the dimension of "pain/discomfort" by the multivariate analysis (p < 0.001). Factors affecting QOL improvement were FRAX value without BMD, age, glucocorticoid use, ischemic heart disease, hip osteoarthritis, and pain. The incidence rate of drug-related adverse events was 4.72 % (95 % confidence interval 3.63-6.02 %). Risedronate at 17.5 mg/week improved the QOL in patients with osteoporosis among Japanese women, and comorbidity factors decreased the effects.

Aspirin-intolerant asthma (AIA) assessment using the urinary biomarkers, leukotriene E4 (LTE4) and prostaglandin D2 (PGD2) metabolites.

The clinical syndrome of aspirin-intolerant asthma (AIA) is characterized by aspirin/nonsteroidal anti-inflammatory drug intolerance, bronchial asthma, and chronic rhinosinusitis with nasal polyposis. AIA reactions are evidently triggered by pharmacological effect of cyclooxygenase-1 inhibitors. Urine sampling is a non-invasive research tool for time-course measurements in clinical investigations. The urinary stable metabolite concentration of arachidonic acid products provides a time-integrated estimate of the production of the parent compounds in vivo. AIA patients exhibits significantly higher urinary concentrations of leukotriene E(4) (LTE(4)) and 1,15-dioxo-9α-hydroxy-2,3,4,5-tetranorprostan-1,20-dioic acid (tetranor-PGDM), a newly identified metabolite of PGD(2), at baseline. This finding suggests the possibility that increased mast cell activation is involved in the pathophysiology of AIA even in a clinically stable condition. In addition, lower urinary concentrations of primary prostaglandin E(2) and 15-epimer of lipoxin A(4) at baseline in the AIA patients suggest that the impaired anti-inflammatory elements may also contribute to the severe clinical outcome of AIA. During the AIA reaction, the urinary concentrations of LTE(4) and PGD(2) metabolites, including tetranor-PGDM significantly and correlatively increase. It is considered that mast cell activation probably is a pathophysiologic hallmark of AIA. However, despite the fact that cyclooxygenease-1 is the dominant in vivo PGD(2) biosynthetic pathway, the precise mechanism underlying the PGD(2) overproduction resulting from the pharmacological effect of cyclooxygenease-1 inhibitors in AIA remains unknown. A comprehensive analysis of the urinary concentration of inflammatory mediators may afford a new research target in elucidating the pathophysiology of AIA.

Increase in salivary cysteinyl-leukotriene concentration in patients with aspirin-intolerant asthma.

BACKGROUND: Cysteinyl-leukotrienes (CysLTs; LTC4, LTD4, and LTE4) play a considerable role in the pathophysiology of aspirin-intolerant asthma (AIA). Saliva has recently been validated as novel, simple, and noninvasive method for investigating inflammation in patients with asthma. The aim of this study is to clarify the molecular species of CysLT in saliva and to evaluate the CysLT and LTB4 concentrations in saliva in AIA patients. We also examined how the CysLT concentration in saliva reflects that of their corresponding urinary metabolite. METHODS: We preformed an analytical cross-sectional study. CysLT and LTB4 concentrations in saliva were quantified by enzyme immunoassay (EIA) following purification by high-performance liquid chromatography (HPLC). RESULTS: 1. When analyzed by EIA in combination with HPLC, saliva was found to consist of LTC4, LTD4 and LTE4 in similar amounts. 2. In saliva analysis among the three groups (AIA patients, aspirin-tolerant asthma [ATA] patients, and healthy subjects), both the concentrations of CysLTs and LTB4 were significantly higher in AIA patients than in ATA patients and healthy subjects. 3. We found significant correlations between CysLT concentration and LTB4 concentration in saliva in each group. 4. No significant correlation was found between the concentration of LTE4 in urine and that of CysLTs in saliva. CONCLUSIONS: In this study, we found higher concentrations of CysLTs and LTB4 in saliva from AIA patients than in saliva from ATA patients, suggesting that the quantification of CysLT and LTB4 concentrations in saliva may be another diagnostic strategy for AIA.

[A case of severe influenza (H1N1) 2009 virus pneumonia identified by virus culture instead of PCR].

A 70-year-old man was being treated for asthma and chronic obstructive pulmonary disease, which had been well controlled. He was seen at our emergency outpatient department on October 24, 2009, for respiratory distress and mild fever. Point-of-care testing for influenza, general bacteria, and acid-fast bacilli in the sputum, were negative. With antibiotics ineffective, his respiratory status worsened, requiring him to be intubated and ventilated mechanically. Steroid pulse therapy temporarily improved his condition, as confirmed by imaging studies, but he died on hospital day 38. Polymerase chain reaction (PCR) analysis of tracheal secretion and bronchial washings collected on hospital day 14 and 21 were negative for influenza (H1N1) 2009 virus, which was identified in a subsequent culture. Negative results for reverse transcriptase-PCR analysis leave (H1N1) 2009 virus unable to be diagnosed clinically. Culture tests and repeated PCR analysis have been done in cases of strongly suspected clinical infection to confirm results. Our case, in which the virus was identified by culture, suggests that the viral load may have been too low or the time of culture inappropriate.

Profile of eicosanoid generation in aspirin-intolerant asthma and anaphylaxis assessed by new biomarkers.

BACKGROUND: It has recently demonstrated that a free radical-mediated pathway generates prostaglandins (PGs) and the corresponding prostaglandin enantiomers (ent-PGs). Aspirin-intolerant asthma and anaphylaxis accompany PGD(2) overproduction, possibly associated with mast cell activation via the COX pathway. However, free radical-mediated PG generation in the pathophysiology of these diseases, which can be demonstrated by measuring urinary ent-PGF(2)alpha, has not been reported. OBJECTIVES: To evaluate the characteristic profile of eicosanoid generation via the COX and/or free radical-mediated pathway underlying aspirin-intolerant asthma and anaphylaxis. METHODS: A comparative group analysis consisted of asthma (n = 17) and anaphylaxis (n = 8, none with aspirin-induced anaphylaxis) cases. Urinary eicosanoid concentrations were quantified as follows: 2,3-dinor-9alpha,11beta-PGF(2) by gas chromatography-mass spectrometry; leukotriene E(4), 9alpha,11beta-PGF(2), and PGs by enzyme immunoassay. RESULTS: 2,3-Dinor-9alpha,11beta-PGF(2) is a more predominant PGD(2) metabolite in urine than 9alpha,11beta-PGF(2). At baseline, the aspirin-intolerant asthma group (n = 10) had significantly higher leukotriene E(4) and lower PGE(2) concentrations in urine than the aspirin-tolerant asthma group. During the reaction, the urinary concentrations of leukotriene E(4) and PGD(2) metabolites correlatively increased, but with markedly different patterns of the mediator release, in the aspirin-intolerant asthma group and the anaphylaxis group, respectively. The urinary PGD(2) metabolites and primary PGs were significantly decreased in the aspirin-tolerant asthma group. Urinary ent-PGF(2)alpha concentrations were significantly increased in the anaphylaxis group but not the aspirin-intolerant asthma group. CONCLUSIONS: When assessed by urinary 2,3-dinor-9alpha,11beta-PGF(2), PGD(2) overproduction during aspirin-intolerant bronchoconstriction was clearly identified, regardless of COX inhibition. It is evident that free radical-mediated PG generation is involved in the pathophysiology of anaphylaxis.

CD203c expression on human basophils is associated with asthma exacerbation.

BACKGROUND: CD203c is a basophil cell surface marker used to diagnose and monitor various allergic diseases, but its relationship to asthma is not clear. OBJECTIVE: We determined whether CD203c expression levels are associated with stable and exacerbated asthma. METHODS: We used flow cytometry to compare spontaneous expression levels of surface markers on basophils from patients with stable or exacerbated asthma and from healthy subjects. Longitudinal changes in these expression levels were measured after basophil stimulation by IgE-dependent or IgE-independent mechanisms and compared with patients' asthma status. RESULTS: Spontaneous expression levels of CD203c were significantly higher on basophils from patients with asthma exacerbation than patients with stable asthma or healthy subjects. In contrast, no differences in spontaneous expression levels of CD63 or CD69 were observed among the 3 groups. Anti-IgE-induced expression of CD203c significantly increased in basophils during asthma exacerbation (P = .005). Low concentrations of Dermatophagoides pteronyssinus or IL-3 induced higher expression levels of CD203c during asthma exacerbation than during clinical improvement; induction of CD203c expression by these antigens therefore correlates with asthma control. In the patients with clinical improvement, there was a correlation between spontaneous CD203c expression levels and the percent predicted values of FEV(1) (r = -0.761; P = .022). CONCLUSION: Asthma exacerbation was accompanied by increased expression of CD203c on basophils that decreased significantly during remission. Basophil expression levels of CD203c might therefore be used to monitor asthma in patients.

Paragonimiasis in a person whose symptoms were shown 22 years after emigrating to Japan from Laos.

We report a patient, a 52-year-old man from Laos, who had come to Japan at 30 years of age, but had maintained a habit of eating raw freshwater crabs. The patient visited a physician for left chest pain in January 2007. Infiltration and mass-like shadows were noted in the left superior and inferior lobes on chest X-ray. Diagnosis could not be made by bronchial brushing, but eggs were present in sputum cytology 3 days after bronchoscopy. Therefore, paragonimiasis was diagnosed. The peripheral eosinophil count had increased to 2550/µl and the serum IgE level was elevated, at 71000 IU/ml. Multiple-dot enzyme-linked immunosorbent assay (ELISA) for specific IgG antibodies in serum was positive for Paragonimus westermani and P. miyazakii. Paragonimiasis may have been caused by the style of Laotian cooking without heating. Because the habit of eating raw freshwater crabs is common in Laos, Laos is one of the countries where paragonimiasis is prevalent. For patients from Laos with lung diseases, differentiation including paragonimiasis is required.

Disseminated cryptococcal infection with eosinophilia in a healthy person.

A 23-year-old man with no recent medical history was hospitalized complaining of high fever and cough. In addition to very marked eosinophilia, chest X-ray revealed extensive bronchovascular bundle thickening. Transbronchial lung biopsy (TBLB) showed moderate eosinophil infiltration. Cryptococcus neoformans infection was diagnosed, based on blood culture, cerebrospinal fluid culture, urine culture, and lung biopsy specimens. The eosinophilia was successfully alleviated by treatment for cryptococcal meningitis. Furthermore, cryptococcal sepsis resolved with amphotericin B and 5-flucytosine treatment. Eosinophilia commonly occurs following chronic Aspergillus infection, but the present case suggests the involvement of Cryptococcus in another mechanism for eosinophilia.

[Case of pulmonary MALT lymphoma with follow-up imaging for 10 years].

Although abnormal shadow in the left upper lung of an 84-year-old male patient was confirmed in an examination in November 1996, follow-up observation was discontinued. In July 2006, he first visited our department with a chief complaint of shortness of breath, and was hospitalized because of an abnormal shadow in the left upper lung field and left pleural effusion. Since atypical lymphocytes were found in the pleural effusion, and positive cellular surface markers CD19 and 20, and chromosomal aberration of t (11 ; 18) (q22 ; q21) were confirmed, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) was diagnosed. Transbronchial lung biopsy of the left upper lobe confirmed small lymphocyte-like cellular infiltration, as seen in the pleural effusion, and CD20 immunostaining was positive, leading to the diagnosis of MALT lymphoma. In addition, serum immunoelectrophoresis demonstrated the development of macroglobulinemia as a complication. This case is valuable as changes diagnostic image over 10 years can be compared.

Efficacy of corticosteroids in the treatment of community-acquired pneumonia requiring hospitalization.

BACKGROUND: Recent studies suggested that administration of corticosteroids may improve clinical outcomes in patients with severe pneumonia. OBJECTIVES: The aim of this study was to assess the effectiveness of corticosteroids as an adjunctive therapy in community-acquired pneumonia (CAP) requiring hospitalization. DESIGN AND SETTING: An open label, prospective, randomized control study was conducted from September 2003 to February 2004 in a community general hospital in Japan. PATIENTS: Thirty-one adult CAP patients who required hospitalization were enrolled. MEASUREMENTS AND RESULTS: Fifteen patients received 40 mg of prednisolone intravenously for 3 days (steroid group). Sixteen patients did not receive prednisolone (control group). Both groups were also evaluated for their adrenal function. The primary endpoint was length of hospital stay. Secondary endpoints were duration of intravenous (IV) antibiotics and time required to stabilize vital signs. Both groups demonstrated similar baseline characteristics and length of hospital stay, and yet a shorter duration of IV antibiotics was observed in the steroid group (p < 0.05). In addition, vital signs were stabilized earlier in the steroid group (p < 0.05). These differences were more prominent in the moderate-severe subgroup but not as significant in the mild-moderate subgroup. The prevalence of relative adrenal insufficiency (RAI) in both groups was high (43%), yet there was no difference in baseline characteristics between patients, with or without RAI. In multiple regression models, RAI seemed to have no influence on clinical courses. CONCLUSIONS: In moderate-severe CAP, administration of corticosteroids promotes resolution of clinical symptoms and reduces the duration of intravenous antibiotic therapy.

Rapidly progressive invasive pulmonary aspergillosis in a diabetic man.

A 45-year-old man was admitted to our hospital with high fever and a large amount of gray sputum. His initial chest X-ray showed broncho-bronchiolitis and thickening of the large bronchus, and he was subsequently diagnosed with pulmonary aspergillosis based on his sputum culture, polymerase chain reaction for Aspergillus fumigatus, and mannan antigen for Aspergillus. His immune responses, including neutrophil phagocytosis function and neutrophil sterilizing function, were normal as far as we could determine. He was treated with itraconazole, amphotericin B, and meropenem trihydrate, but died of respiratory failure on the twenty-fifth hospital day. Chest X-ray showed rapidly progressive invasive shadows in both lung fields, resulting in multiple cavity formation. This was a rare case of invasive pulmonary aspergillosis in a diabetic man with normal neutrophil phagocytosis function and neutrophil sterilizing function.